Policy Statement

The Agriculture Select Agent Services (AgSAS) regulates the possession, use, and transfer of biological agents listed in 7 C.F.R. Part 331 and 9 C.F.R. Part 121 that have the potential to pose a severe threat to animal or plant health or animal or plant products (select agents and toxins).

Background:

AgSAS received requests to remove the requirement* for live bird lethality testing used to determine the pathogenicity characteristics of reverse genetically derived viruses, for avian influenza viruses that undergo a manipulation process that alters the pathogenicity of the virus from high to low.

the backbone strain is a PR8 or similar human vaccine strain previously demonstrated to have limited to no replication in poultry, regardless of the HA gene; and

the H5/H7 cleavage site has been altered from highly pathogenic avian influenza (HPAI) to low pathogenic avian influenza (LPAI); and

viruses used for gene inserts have been well characterized as LPAI prior to use in reverse genetically derived processes.

In lieu of the live bird lethality testing, AgSAS will require all reverse genetically derived H5/H7 viruses with PR8 or similar human vaccine strain backbone to:

Confirm by genetic sequencing that the amino acid sequence at the HA cleavage site is compatible with only LPAI viruses; and

Demonstrate functionality as a LPAI virus either by cell culture system with/without exogenous trypsin, or in-vivo test in chickens by the intravenous pathogenicity index (IVPI) per World Organisation for Animal Health (OIE) standards.